These studies seek to define and describe the molecular mechanisms whereby the major catabolic (i.e. energy-releasing) pathways of intermediary metabolism are controlled, and to investigate the ways in which these controls are altered in old-age. Such alterations are considered to underlie the decreased ability of senescent animals (including humans) to withstand environmental stresses (e.g. starvation, severe cold). Current investigations feature: (1) the control of concentration of pyruvate dehydrogenase and 2-oxoglutarate dehydrogenase activities by micromolar concentrations of Ca++ ions; (2) the transport of Ca++ ions into and out of heart mitochondria, at very low concentrations and the impact of aging; (3) the control of pyruvate dehydrogenase in skeletal muscle and the effect of fatty acid oxidation; and (4) the measurement of the key rate-limiting enzymes of fatty acid ozidation and the tricarboxylate cycle in heart, diaphragm and soleus muscles, in young adult and senescent animals.